EP2019097A1 - Verfahren zur Herstellung von (alphaS)-alpha-(2-Methylpropyl)-2-(1-piperidinyl)benzenmethanamin - Google Patents

Verfahren zur Herstellung von (alphaS)-alpha-(2-Methylpropyl)-2-(1-piperidinyl)benzenmethanamin Download PDF

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Publication number
EP2019097A1
EP2019097A1 EP08011984A EP08011984A EP2019097A1 EP 2019097 A1 EP2019097 A1 EP 2019097A1 EP 08011984 A EP08011984 A EP 08011984A EP 08011984 A EP08011984 A EP 08011984A EP 2019097 A1 EP2019097 A1 EP 2019097A1
Authority
EP
European Patent Office
Prior art keywords
formula
piperidinyl
methylpropyl
benzenemethanamine
repaglinide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08011984A
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English (en)
French (fr)
Inventor
Reddy Karuru Mallikarjuna
Mitra Jayati
Meenakshisunderam Sivakumaran
Dandala Ramesh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aurobindo Pharma Ltd
Original Assignee
Aurobindo Pharma Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Aurobindo Pharma Ltd filed Critical Aurobindo Pharma Ltd
Publication of EP2019097A1 publication Critical patent/EP2019097A1/de
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

Definitions

  • the present invention relates to an improved process for the preparation of ( ⁇ S)- ⁇ -(2-methylpropyl)-2-(1-piperidinyl)benzenemethanamine of Formula I, which is a key intermediate for the synthesis of repaglinide of Formula II,
  • Repaglinide is chemically known as 2-ethoxy-4-[2-[[(1 S )-2-methyl-1-[2-(1-piperidinyl)-phenyl]butyl]amino]-2-oxoethyl]benzoic acid.
  • Repaglinide is marketed under the trade name PRANDIN.
  • Repaglinide is a hypoglycemic agent useful for the treatment of type II non-insulin dependent diabetes mellitus.
  • US 2007/0123564 A1 discloses a process to prepare repaglinide by resoluting the amine using a chiral reagent.
  • the process is as shown below: wherein A represents a chiral reagent selected from optically active carboxylic acids, e.g. mandelic acid, which is optionally substituted at the phenyl ring, optically active camphorsulphonic acid, optically active tartaric acid and optically active substituted tartaric acid or also optically active phosphoric acid, e.g. 1,1'-binaphthalin-2,2'-diyl-phosphoric acid.
  • A represents a chiral reagent selected from optically active carboxylic acids, e.g. mandelic acid, which is optionally substituted at the phenyl ring, optically active camphorsulphonic acid, optically active tartaric acid and optically active substituted tartaric acid or also optically active phosphoric acid, e.g. 1,1'-bina
  • the inventors have developed a more convenient process in comparison to the methods described above, where the amine has to be reacted with a substituted benzyl group and finally deprotected, which is cumbersome on a larger scale.
  • the objective of the present invention is to provide a process for preparing pure amine, which is commercially feasible with high yield and acceptable purity suitable for making repaglinide.
  • Another objective of the present invention is that the process results in higher yields compared to the methods already disclosed in prior art for the manufacture of repaglinide.
  • the present invention relates to an improved process for the preparation of ( ⁇ S)- ⁇ -(2-methylpropyl)-2- (1-piperidinyl)benzenemethanamine of Formula I which comprises,
  • the present invention also relates to further conversion of the amine of Formula I to repaglinide of Formula II.
  • the present invention relates to a process for the preparation of ( ⁇ S)- ⁇ -(2-methylpropyl)-2-(1-piperidinyl)benzenemethanamine of Formula I, which comprises dissolving racemic amine in a solvent or a mixture of solvents at temperatures ranging from 0°C to 100°C, preferably at ambient temperature 25-30°C.
  • the solvents are selected from aliphatic esters such as ethyl acetate, ketones such as acetone, alcohols such as methanol, and ethers such as t-butyl methyl ether, preferably acetone.
  • the (4 R )-1-benzoyl-4-hydroxy-L-proline can be isolated from the aqueous solution by acidification and recycled, which further adds to the efficiency of the process.
  • the ( ⁇ S)- ⁇ -(2-methylpropyl)-2- (1-piperidinyl)benzenemethanamine of Formula I is further converted to repaglinide of Formula II, by condensing with 3-ethoxy-4-(ethoxycarbonyl)benzene acetic acid.
  • the present invention also relates to the novel diastereomeric salt of Formula IV

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
EP08011984A 2007-07-25 2008-07-03 Verfahren zur Herstellung von (alphaS)-alpha-(2-Methylpropyl)-2-(1-piperidinyl)benzenmethanamin Withdrawn EP2019097A1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IN1607CH2007 2007-07-25

Publications (1)

Publication Number Publication Date
EP2019097A1 true EP2019097A1 (de) 2009-01-28

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Application Number Title Priority Date Filing Date
EP08011984A Withdrawn EP2019097A1 (de) 2007-07-25 2008-07-03 Verfahren zur Herstellung von (alphaS)-alpha-(2-Methylpropyl)-2-(1-piperidinyl)benzenmethanamin

Country Status (1)

Country Link
EP (1) EP2019097A1 (de)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2364977A1 (de) 2010-01-26 2011-09-14 Reuter Chemische Apparatebau KG Verfahren zur Enantiomerenanreicherung von 3-Methyl-1-(2-Piperidinphenyl)-1-Butylamin
CN102633750A (zh) * 2012-03-26 2012-08-15 浙江昂利康制药有限公司 一锅法合成治疗糖尿病的药物瑞格列奈
CN102731436A (zh) * 2012-04-09 2012-10-17 海南中化联合制药工业股份有限公司 一种瑞格列奈的制备及精制方法
CN103012319A (zh) * 2011-09-20 2013-04-03 浙江九洲药业股份有限公司 瑞格列奈中间体的合成工艺改进
CN103664828A (zh) * 2012-09-12 2014-03-26 高瑞耀业(北京)科技有限公司 制备高纯度瑞格列奈的方法
CN105384708A (zh) * 2015-10-21 2016-03-09 河南普瑞制药有限公司 一种（s）-（+）-1-（2-哌啶苯基）-3-甲基正丁胺的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993000337A1 (de) * 1991-06-21 1993-01-07 Dr. Karl Thomae Gmbh (s)(+)-2-äthoxy-4-[n-[1-(2-piperidino-phenyl)-3-methyl-1-butyl]aminocarbonylmethyl]-benzoesäure
US6143769A (en) 1983-12-30 2000-11-07 Karl Thomae Gmbh Phenylacetic acid benzylamides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6143769A (en) 1983-12-30 2000-11-07 Karl Thomae Gmbh Phenylacetic acid benzylamides
WO1993000337A1 (de) * 1991-06-21 1993-01-07 Dr. Karl Thomae Gmbh (s)(+)-2-äthoxy-4-[n-[1-(2-piperidino-phenyl)-3-methyl-1-butyl]aminocarbonylmethyl]-benzoesäure
EP0589874B1 (de) 1991-06-21 1999-09-08 Boehringer Ingelheim Pharma KG Verwendung von (s)(+)-2-äthoxy-4-[n-[1-(2-piperidino-phenyl)-3-methyl-1-butyl]aminocarbonylmethyl]-benzoesäure zur herstellung eines langzeitantidiabetikums

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF MEDICINAL CHEMISTRY, vol. 41, 1998, pages 5219
N. KOLLA ET AL, CHIMIA, vol. 60, no. 9, 2006, pages 593 - 597, XP002507261 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2364977A1 (de) 2010-01-26 2011-09-14 Reuter Chemische Apparatebau KG Verfahren zur Enantiomerenanreicherung von 3-Methyl-1-(2-Piperidinphenyl)-1-Butylamin
CN103012319A (zh) * 2011-09-20 2013-04-03 浙江九洲药业股份有限公司 瑞格列奈中间体的合成工艺改进
CN103012319B (zh) * 2011-09-20 2015-06-10 浙江九洲药业股份有限公司 瑞格列奈中间体的合成工艺改进
CN102633750A (zh) * 2012-03-26 2012-08-15 浙江昂利康制药有限公司 一锅法合成治疗糖尿病的药物瑞格列奈
CN102731436A (zh) * 2012-04-09 2012-10-17 海南中化联合制药工业股份有限公司 一种瑞格列奈的制备及精制方法
CN103664828A (zh) * 2012-09-12 2014-03-26 高瑞耀业(北京)科技有限公司 制备高纯度瑞格列奈的方法
CN105384708A (zh) * 2015-10-21 2016-03-09 河南普瑞制药有限公司 一种（s）-（+）-1-（2-哌啶苯基）-3-甲基正丁胺的制备方法

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